Safety study of ivabradine in severe burn patients

JRCT ID: jRCTs031240390

Registered date:01/11/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Severe extensive burns (2nd and 3rd degree total burn area >= 20 %)
• Date of first enrollment: 01/11/2024
• Target sample size: 5
• Study type: Interventional

Intervention(s)

In patients with extensive burns with a total burn area >= 20 % and a heart rate > 75 beats/min, ivabradine should be started at a dose of 2.5 mg twice daily by mouth (or tube) in the morning and evening. If the heart rate exceeds 75 beats/minute for at least 2 weeks after initiation of treatment, the dose is increased to 5 mg twice daily in the morning and evening.
If the heart rate falls below 50 beats/minute, discontinue administration. If heart rate exceeds 75 beats/minute, resume with oral (or tube) doses of 2.5 mg twice daily in the morning and evening.

Outcome(s)

• Primary Outcome: Frequency of hypotension (systolic pressure less than 90 mmHg or diastolic pressure less than 50 mmHg)

Secondary Outcome

Adrenaline, insulin, ketone bodies (acetoacetate, beta hydroxybutyrate as markers of metabolism, O2 and CO2 in exhaled air, blood glucose, free fatty acids, lactic acid, lipid metabolic indices (TG, CHO, LDL, VLDL, HDL)
Frequency of bradycardia (50 beats/minute)
Evaluation of liver, renal, and cardiac function
Incidence rate of hypotensive shock
Presence or absence of arrhythmias such as atrioventricular block, atrial fibrillation, QT prolongation, etc.
Light sensitivity, foggy vision, or no light sensitivity
Intravenous fluid requirements and contents during ICU/HCU admission, urine volume, weight change, change in serum albumin level, albumin dosage, length of stay in ICU/HCU and length of hospital stay.
Amount of calories consumed by indirect calorimetry
Compare the above items with patients with BI of 20 or more treated at this hospital during the past 5 years.
Biomarkers (TNF-alpha, ANP, BNP, IL-6, IL-8, IL-10, TGF-beta)
Burn site healing, presence of wound infection, presence of surgical procedures, pain assessment

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Patients who meet all the following criteria will be considered
1) Burn patients aged 18 years and older with at least 20% of total burn area(2nd and 3rd degree), (regardless of gender)
2) Patients who are able to administer the drug orally or by gavage
3) Patients with a sustained resting (sedated)heart rate of 75 beats/minute or greater, and whose physician has determined that ivabradine can be administered.
4) Sinus rhythm
5) Patients with no history of cardiac disease
6) Patients who have been fully informed of the study and who have given written consent of their own free will or that of a surrogate, based on a thorough understanding of the study.

Exclude criteria

Patients who violate any of the following will not be included in this study
1) Patients with a history of hypersensitivity to ivabradine
2) Patients on Clozapine
3) Persistent circulatory failure unresponsive to supplemental fluids or standard vasoactive agents
4) Patients with severe hypotension (systolic pressure less than 90 mmHg or diastolic pressure less than 50 mmHg despite infusion load and standard vasoactive drugs)
5) Patients with severe hepatic impairment (Child-Pugh C)
6) Patients with right heart failure due to pulmonary hypertension
7) Patients receiving ritonavir-containing products, josamycin, itraconazole, clarithromycin, cobicistat-containing products, voriconazole, encitrelvir fumarate, verapamil, diltiazem
8) Women who are pregnant or may become pregnant
9) Lactating women
10) Other patients deemed inappropriate as subjects by the principal investigator (or subinvestigator)

Related Information

• Primary Sponsor: INOUE YOSHIAKI
• Source(s) of Monetary Support: Japan Society for the Promotion of Science,University of Tsukuba Hospital